The functions of SV40 and polyoma large tumor antigens are required for viral replication. However, the SV40 large tumor antigen is also needed for virus-mediated malignant cell transformation, a function that the polyoma large tumor antigen lacks. The long term goal of this research effort is to investigate the interaction of these regulatory proteins with the virus and host cell genomes in order to understand viral induced carcinogenesis. The structure and modifications of these proteins will be analyzed with particular respect to their sequence specific high affinity for viral DNA. In addition, the ability of wild type and mutant SV40 tumor antigens to bind to cellular DNA will be investigated in order to determine whether this is related to transformation function. Polyoma tumor antigen will be produced in sufficiently large quantities to determine its binding to sites on viral DNA and its enzymatic activities. Deletion mutants of polyoma large tumor antigen will be created in order to identify functional domains of the protein. The interactions of SV40 and polyoma tumor antigens with both viral genomes will be studied.